This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The objective of this research is to improve our understanding of lung function during exercise in asthmatics. Bronchial asthma is the most prevalent chronic disease worldwide. A principal feature of asthma is the presence of a variable degree of airway narrowing, even in the absence of recent exposure to asthmatic triggers. The airways of most asthmatics are also hyperresponsive to exercise, in which they bronchoconstrict after completion of the exercise. In light of recommendations by several health organizations that humans engage in regular physical activity as part of a healthy lifestyle, the fact that exercise triggers bronchoconstriction in most asthmatics is discouraging. Furthermore, it is often assumed that exercise-induced asthma has a negative effect on exercise capacity. Exercise, however, is known to cause bronchodilation, and thus improved airway function during the exercise. It is therefore possible that a protective effect of exercise on airway function prevents compromised exercise capacity, irrespective of the state of airway function present before and after exercise. The aim of this proposal is to determine the effects of alterations in pre-exercise airway mechanical function on airway function during and after exercise in asthmatic humans. In Specific Aim 1, we will determine the effects of improved and worsened pre-exercise airway mechanical function on airway function during exercise in asthmatic humans. In Specific Aim 2, we will determine the effects of altered pre-exercise airway mechanical function on the amount of airway narrowing that occurs after exercise in asthmatic humans. Subjects will complete cycling exercise tests to exhaustion on four separate occasions. Prior to each exercise test, a different experimental intervention will be used to improve or worsen airway mechanical function or to act as placebo or control. The interventions will include: 1) an intervention to improve airway function, 2) an intervention to impair airway function, 3) a placebo for the impaired airway function intervention, and 4) a control trial. Detailed analyses of airway mechanical function, including calculation of pulmonary resistance, will be assessed before, during, and after exercise. The responses will be compared between the exercise studies to determine the influence of pre-exercise airway mechanical function on airway function during and after exercise in asthmatic humans.